The invention relates to “active implantable medical devices” as defined by Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities. It relates more specifically to implantable devices delivering pacing therapies to the nervous system, including stimulation of the vagus nerve. This type of stimulation will be here designated as “neurostimulation” or “VNS stimulation” (Vagus Nerve Stimulation).
The nervous system stimulation is a recognized therapy in respect of many disorders such as epilepsy, pain, heart failure, sleep apnea, obesity, etc. For the treatment of disorders such as heart failure, epilepsy or obesity, the used devices typically include a lead provided with an electrode implanted on the vagus nerve (called “VNS lead”) and a generator supplying pulses VNS on this electrode.
In some therapies, the vagus nerve is stimulated synchronously with the cardiac rhythm. The device then including methods for collecting myocardium depolarization wave, typically methods for collecting an ECG by a subcutaneous electrode, or an EGM by an electrode implanted on or in the myocardium. VNS stimulation then consists in delivering a “stimulation profile” including bursts of a few VNS pulses triggered in synchronism with the cardiac rhythm. This type of VNS stimulation is particularly well suited to the treatment of heart disease, particularly in patients at risk of heart failure, when the vagus nerve stimulation acts on cardiovascular function by reducing heart rate, reducing myocardial contractility and increased diastole duration, which can help reduce the development of cardiac remodeling which may lead to an aggravated heart failure state.
In other types of therapy, the VNS stimulation profile consists of bursts or high frequency repetitive train pulses (several tens of hertz) produced during periods of “activity” of a few tens of seconds interspersed by periods of “inactivity” of a few minutes during which the stimulus is no longer issued.
In general, in the case of heart diseases, especially heart failure, the implantation of a cardiac device is frequently indicated, whether it is a pacemaker (PM, Pacemaker), an implantable Cardioverter/Defibrillator (ICD) or a resynchronizer (a device for Cardiac Resynchronization Therapy (CRT)). This stimulation, operating by delivery of pulses to the myocardium, for example by methods of an endocardial lead, will be designated hereafter as “cardiac stimulation” or “CRM (Cardiac Rhythm Management) stimulation”. The patients already implanted or candidates for implantation with such an implantable cardiac device could also benefit from a VNS stimulation.
To either deliver CRM stimulation or VNS stimulation from the same implant, U.S. Pat. No. 7,660,628 proposes to provide an apparatus including a circuit for generating on the same channel either CRM pulses or VNS pulses. The pulse generator is common, but it is controlled with pulse amplitude parameters (that is to say, of voltage supplied to the electrodes) and with pulse repetition frequency which depend on the selected CRM or VNS function.
The application to the vagus nerve of pulses generated by such a device, however, is likely to produce a highly variable physiological effect, because the nervous electrode/vagus nerve interface is much more unstable than the cardiac electrode/myocardium interface. Indeed, significant changes in the biological impedance at the interface are met, which, for the same stimulation voltage, leads to widely varying currents flowing in the regions of the vagus nerve to be stimulated, with the result of physiological effects which can vary erratically due to the variable and unpredictable intensities. Specifically, the teachings of this document do not provide a device providing a satisfactory VNS stimulation, even if the cardiac stimulation generator is programmed to deliver pulses at a rate and in a profile suitable for VNS stimulation.
U.S. Pat. No. 8,478,404 describes another combination device, including a separate circuit to generate on a single channel either CRM pulses or VNS pulses. The pulse generator includes circuitry for controlled charge and discharge of a capacitor, with a switchable current source connected in series in the discharge circuit. In the case of CRM stimulation, the discharge path bypasses that current source which is neutralized, so that the capacitor discharge voltage is directly applied to the electrodes connected to the generator. In contrast, in the case of VNS stimulation, the current source inserted in the discharge path of the capacitor has the effect of regulating the current of the delivered pulse, and therefore allows accurate adjustment of the amount of charge applied to the nerve in contact with the electrodes.
It is thus possible to combine in one device the CRM stimulation and VNS stimulation functionalities. However, the device is initially specifically designed for this dual function and at the cost of increased complexity (presence of a current source, various switching circuit elements, etc.) therefore with high overall cost, both in the development stage and during manufacturing. The need therefore remains to have a simplified mixed CRM/VNS generator, including at the hardware level, with conventional circuits based on the controlled charge/discharge of a capacitor but neither implementing current sources nor additional switching elements.
Thus, a first object of the invention is to reduce the unit cost of the devices for VNS stimulation, using for this a hardware part similar to what is already included in an implantable pacemaker, by adjusting the equipment for implementation without significant additional cost.
Another aspect of the present invention results in that in some patients (a relatively large proportion, around 30% of these patients) implanted with a cardiac resynchronizer (CRT device) do not respond to CRT therapy and implantation of the device has provided no positive effect. However, these patients could be responders to VNS therapy, but in this case, it would be necessary to use another device, thereby requiring further surgery to explant the CRT device and implant a VNS device, with all the disadvantages and the costs associated with such an intervention.
Another aim of the invention is to provide a usable VNS generator for patient categories described above, in particular for patients already implanted with a pacemaker/defibrillator that could be subjected, with a benefit, to an additional VNS stimulation. For these patients, it would be preferable to have a device, including a generator, combining in one housing both (cardiac and VNS) therapies, with a significant advantage both for patient comfort and for the cost supported by the health system.
The basic idea of the invention is to use a pacemaker generator, that is to say, originally intended for stimulation of one or more cavities (ventricle or atrium) of the myocardium, and to adapt this device to make it capable of vagus nerve stimulation instead of stimulating a ventricle or an atrium.
As explained in the detailed description, this adaptation can be achieved by change of the cardiac generator control software only. Thus, the hardware of the VNS stimulation device being identical to that which already exists for a pacemaker, VNS stimulation may, by applying the invention, be implemented without significant additional cost. Notably, VNS stimulation may be implemented without the addition of any current source or additional switching elements while keeping the conventional architecture of voltage controlled charge/discharge circuits.
In particular, as will also be seen, this adaptation to transform a pacemaker into a VNS stimulator can be performed even in a patient already implanted, retaining the same generator—therefore without explantation of the device—and by connecting to one of the generator channels (e.g. the atrial channel) a VNS lead instead of a cardiac lead. Another channel connected to a cardiac lead (e.g. the ventricular channel connected to an endocardial lead) may be optionally used for the synchronization of the VNS pulses on the cardiac rhythm, if such a neurostimulation profile is selected.
This principle is not only applicable to a simple pacemaker but also to an implantable defibrillator (thus retaining the ability to deliver a antitachycardia shock therapy). It is also applicable to a resynchronizer (CRT device), by reusing one of the ventricular channels to adapt it to the purposes of VNS stimulation, another ventricular channel being retained for the collection of a synchronization signal of the VNS therapy and possibly being used for the delivery of pacing pulses in conjunction with VNS stimulation.
This same principle can be extrapolated to patients who fall under such indication, the substitution of a VNS stimulation to cardiac stimulation, all channels of the pacemaker generator (single, double or triple chambers) being reused as the same number of neurostimulation channels, by connection to one or more respective leads.
Note that if the patient is already implanted, this transformation can be performed without explantation of the generator, the intervention being restricted to the implantation of one or more VNS leads and to their connection to the generator (with or without explantation, if necessary, of the moot cardiac leads).
However, in all these cases, a pacemaker generator is not suitable for the delivery of VNS pulses. Indeed, as explained above, the application to the vagus nerve of pulses at constant voltage produce an unpredictable physiological effect due to widely varying currents circulating in the vagus nerve zones to stimulate, producing physiological effects that can erratically vary due to these variable and unpredictable intensities. Therefore, the simple substitution of a cardiac lead with a VNS lead cannot achieve the desired result, even when the cardiac stimulation generator is programmed to deliver pulses at a rate and with a profile adapted to VNS stimulation.